Ziólkowska B, Höllt V
Physiologisches Institut, Universität München, FRG.
Neurosci Lett. 1993 Jun 25;156(1-2):39-42. doi: 10.1016/0304-3940(93)90434-m.
The influence of the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (dizocilpine), on the haloperidol-induced increase of c-fos mRNA levels in the striata of mice was examined using the quantitative Northern blot analysis method. Administration of haloperidol (1 mg/kg. i.p.) increased striatal c-fos mRNA hybridization signal about 7-fold, as measured 30 min after injection. MK-801 (0.2-4.5 mg/kg, i.p.) dose-dependently reduced this effect of the dopamine antagonist. Higher doses of MK-801 (1.5-4.5 mg/kg) diminished c-fos mRNA increase produced by haloperidol by 80%. Such a marked inhibition of this haloperidol effect by MK-801 has not been previously reported. It suggests that the induction of c-fos gene occurring in the striatum after dopamine D2 receptor blockade is mediated in great part by endogenous glutamate acting at NMDA receptors. Since the c-fos gene protein product (Fos) is a transcription factor, our results also indicate the involvement of glutamate in the regulation of expression of other genes in the striatum.
采用定量Northern印迹分析法，研究了N-甲基-D-天冬氨酸（NMDA）受体拮抗剂MK-801（地佐环平）对氟哌啶醇诱导的小鼠纹状体中c-fos mRNA水平升高的影响。注射氟哌啶醇（1mg/kg，腹腔注射）后30分钟测量，其使纹状体c-fos mRNA杂交信号增加约7倍。MK-801（0.2 - 4.5mg/kg，腹腔注射）剂量依赖性地减弱了多巴胺拮抗剂的这种作用。较高剂量的MK-801（1.5 - 4.5mg/kg）使氟哌啶醇引起的c-fos mRNA增加减少了80%。此前尚未有关于MK-801对氟哌啶醇这种作用的如此显著抑制的报道。这表明多巴胺D2受体阻断后纹状体中发生的c-fos基因诱导在很大程度上是由作用于NMDA受体的内源性谷氨酸介导的。由于c-fos基因蛋白产物（Fos）是一种转录因子，我们的结果还表明谷氨酸参与了纹状体中其他基因表达的调控。
